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Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Integrated Clinicopathological and Multiomic Profiling Reveals MEIS1-rearranged Sarcoma as a Distinct Entity with Two
Maximus C F Yeung1, Philip P C Ip1, Jennifer A Bennett2
1Department of Pathology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
Summary
MEIS1-rearranged sarcomas are a distinct cancer type, often indolent but with a subset showing aggressive behavior. DNA methylation and copy-number variation analysis identified two subgroups, aiding in prognostic stratification.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- MEIS1-rearranged sarcomas are rare mesenchymal neoplasms, primarily affecting genitourinary/gynecologic sites, with limited clinicopathologic and outcome data.
- A subset of these sarcomas exhibit skeletal muscle differentiation, mimicking spindle cell rhabdomyosarcoma.
Purpose of the Study:
- To comprehensively analyze a multi-institutional cohort of MEIS1-rearranged sarcomas.
- To integrate clinicopathologic, genomic, and DNA methylation data for precise classification and prognostic assessment.
Main Methods:
- Analysis of 20 MEIS1-rearranged sarcomas using integrated clinicopathologic review.
- Genomic profiling and DNA methylation analysis were performed.
- Tumor characteristics, fusion partners (NCOA2, NCOA1, FOXO1), and additional genomic alterations (CTNNB1, MDM2) were assessed.
Main Results:
- MEIS1-rearranged sarcomas formed a distinct cluster via DNA methylation profiling, separable into two subgroups (Meth-CNVh and Meth-CNVl).
- The Meth-CNVh subgroup showed higher mitotic rates, necrosis, CTNNB1/MDM2 alterations, and worse overall and disease-free survival.
- Fusions primarily involved MEIS1 with NCOA2 (16/20), with recurrent CTNNB1 mutations (31.6%) and MDM2 amplification (15%).
Conclusions:
- MEIS1-rearranged sarcoma is a distinct entity with variable behavior, ranging from indolent to aggressive.
- DNA methylation and copy-number variation analysis define two prognostic subgroups, enabling risk stratification.
- Identified molecular alterations provide potential therapeutic targets for high-risk MEIS1-rearranged sarcomas.
